Myocardial ischemia occurs when a portion of the heart does not receive sufficient oxygen and energy substrates to meet its demand. This usually occurs because of a blockage in the artery due to either atherosclerotic plaque or thrombus formation. In a myocardial infarction there is an area of injury where the cells, because of lack of blood flow, will die immediately. There is a layer adjacent where there is impaired blood flow that is equivalent to the zone of stasis and there is a more peripheral unaffected zone. Unfortunately the infarcted heart will attempt to increase rate of contracture and overall work to compensate for areas of the heart that are not functioning adequately. Consequentially the areas that are in the “zone of stasis” are called upon to do more work which will increase the energy requirements placed upon them and will subsequently result in further progression of death. If left untreated, this ischemia will lead to an expanding zone of infarction that may eventually extend transmurally across the thickness of the ventricle.
Limiting the degree of infarction resulting from myocardial ischemia is paramount to improving both short- and long-term outcomes in patients. Therefore, in order to salvage this myocardial tissue, timely reperfusion (re-establishment of coronary blood flow) of the tissue must take place. The amount of salvageable tissue within an ischemic zone is dependent on the timeliness of reperfusion. While reperfusion halts the ischemic processes by delivering oxygen and nutrients (including energy substrates), this process also rapidly sets into motion a series of events and cascades that exacerbates injury, extending the area of necrosis beyond that encountered during ischemia alone. Much of this reperfusion injury appears to be inflammatory in nature, but inappropriately directed against host tissues instead of foreign substances. Being able to reduce this reperfusion injury allows for the salvage of the greatest amount of myocardium.
Reperfusion injury manifests itself in a number of ways, including myocardial dysfunction (myocardial stunning), arrhythmias, and a collection of events that result in lethal reperfusion injury. Currently, there are effective pharmacologic therapies to treat reperfusion arrhythmias, and myocardial stunning will generally resolve by itself given time, leaving the mediators of lethal reperfusion injury as the logical targets in an attempt to preserve ischemic-reperfused, but viable tissue.
There are a large number of potential mediators of lethal reperfusion injury including calcium overload, oxygen radicals, changes in osmotic gradients (and subsequent cell swelling), the mitochondrial permeability transition pore, and inflammation (itself a complex set of cascades and mediators including complement activation, leukocyte infiltration and pro-inflammatory cytokines and mediators). In addition, the cardioprotective effects of selective inhibition of any and all of these phenomenon, including antioxidants, sodium-hydrogen exchange inhibitors, anti-inflammatory agents (including adenosine, adhesion molecule antibodies and complement inhibitors) in animal models of myocardial ischemia-reperfusion are known. However, very few have demonstrated any degree of clinical success in people, likely due to the fact that these therapeutics act selectively at a single point within a cascade of events, or on a single facet of a very complex and multifaceted process. Thus, though the application of negative (or sub-atmospheric) pressure therapy to wounded cutaneous and subcutaneous tissue demonstrates an increased rate of healing compared to traditional methods (as set forth in U.S. Pat. Nos. 5,645,081, 5,636,643, 7,198,046, and 7,216,651, as well as US Published Application Nos. 2003/0225347, 2004/0039391, and 2004/0122434, the contents of which are incorporated herein by reference), there remains a need in the art for devices and methods for treating myocardial ischemia. In these type wounds of cutaneous and subcutaneous wounds the screen/dressing can often be easily and non-invasively changed at routine, pre-determined intervals without significant disruption to the healing tissues. However, when techniques are used to treat tissues or organs in which the overlying skin is intact, the overlying skin must be surgically disrupted by the deliberate creation of a wound through the overlying tissue to expose the tissue or organ that was originally injured. The overlying, originally healthy tissues which were disrupted to expose the injured tissue can be sutured closed over top of the injured tissue. This allows for negative pressure treatment of the wounded tissues with restoration of the suprawound tissues. Current commercially available embodiments of negative pressure dressings and cover are not biodegradable or bioresorbable. This lack of biodegradability/bioresorbability necessitates re-opening of the sutured incision, removal of the dressing and cover, placement of a new dressing and cover, and again suturing the incision closed. This sequence would have to be repeated until the original wounded tissue is healed, with one final re-opening of the incision to remove the dressing and cover. Every time the incision is opened to change or remove the dressing and cover, it increases the risk that the site will become infected.